Bone abnormalities in the middle Anisian marine sauropsids from Winterswijk.

While the occurrence of skeletal pathologies in Middle Triassic marine reptiles has been poorly documented until now, massive accumulations of bone remains from the Germanic Basin provide the opportunities for documentation. Herein, we describe skeletal abnormalities in the Middle Triassic bone material from the Vossenveld Formation of Winterswijk, the Netherlands. The aim of the study is to distinguish in the studied bones pathologies resulting from malady or trauma and taphonomic alterations. Furthermore, an attempt was made to assess on how the pathologies also represent paleoecological data. Our survey led to the identification of one broken and healed bone, one case of abnormal coossification, and one case of posttraumatic fibro-osseous dysplasia. While the latter two pathologies give little insight into the ecology and function of the affected animals, the fractured dentary is attributed to Nothosaurus marchicus, a common sauropterygian macropredator. It proves that the individual survived long enough to heal, despite the injury hampering its hunting potential. One abnormally shaped humerus is interpreted as postmortem taphonomic deformation, emphasizing the necessity of utilization of detailed diagnostics to distinguish actual paleopathologies from nonbiological distortion.

Humerus osteology, myology, and finite element structure analysis of Cheloniidae.

Adaptation of osteology and myology lead to the formation of hydrofoil foreflippers in Cheloniidae (all recent sea turtles except Dermochelys coriacea) which are used mainly for underwater flight. Recent research shows the biomechanical advantages of a complex system of agonistic and antagonistic tension chords that reduce bending stress in bones. Finite element structure analysis (FESA) of a cheloniid humerus is used to provide a better understanding of morphology and microanatomy and to link these with the main flipper function, underwater flight. Dissection of a Caretta caretta gave insights into lines of action, that is, the course that a muscle takes between its origin and insertion, of foreflipper musculature. Lines of action were determined by spanning physical threads on a skeleton of Chelonia mydas. The right humerus of this skeleton was micro-CT scanned. Based on the scans, a finite element (FE) model was built and muscle force vectors were entered. Muscle forces were iteratively approximated until a uniform compressive stress distribution was attained. Two load cases, downstroke and upstroke, were computed. We found that muscle wrappings (m. coracobrachialis magnus and brevis, several extensors, humeral head of m. triceps) are crucial in addition to axial loading to obtain homogenous compressive loading in all bone cross-sections. Detailed knowledge on muscle disposition leads to compressive stress distribution in the FE model which corresponds with the bone microstructure. The FE analysis of the cheloniid humerus shows that bone may be loaded mainly by compression if the bending moments are minimized.

Bienestar, apoyo social y contexto familiar de cuidadores de adultos mayores / Well-being, Social Support and Family Context in Caregivers of Older Adults

Objetivo: explorar el papel mediador de la percepción de apoyo social en la influencia que ejerce un contexto familiar problemático sobre el bienestar subjetivo de cuidadores familiares de adultos mayores dependientes funcionales. Método: participó una muestra no probabilística de 464 cuidadores familiares, respondiendo instrumentos psicométricos previamente validados para la población de referencia. Resultados: Análisis Factoriales Confirmatorios indicaron la adecuación de las variables observadas para representar a los constructos bienestar subjetivo, percepción de apoyo social y contexto familiar problemático. Examinando cuatro modelos de ecuaciones estructurales, se identificó un mejor ajuste en el caso de cuidadores que viven con el mayor dependiente funcional, en donde la influencia del contexto familiar estresor sobre el bienestar está mediada por la percepción de apoyo social. Conclusiones: se coincide con la literatura que documenta el efecto buffer del apoyo social, así como también se aportan datos que enriquecen el conocimiento sobre circunstancias familiares y sociales asociadas al bienestar de cuidadores familiares mexicanos.

Objective: to explore the perception of social support as a mediator of the influence from a problematic family context on the well-being of family caregivers of functionally dependent older adults. Method: a non-probabilistic sample of 464 family caregivers participated by answering a psychometric instrument that was previously validated for the population of reference. Results: a series of confirmatory factor analyses indicated the fit of observed variables to represent the constructs of subjective well-being, perception of social support and problematic family context. The case of caregivers who live with the dependent older adult, where the influence of the stressing family context on the caregiver's well-being is mediated by the caregiver's perception of social support was identified as the model with better fit after the review of four different models. Conclusions: this paper agrees with the buffer effect of social support documented in scientific literature, it also provides data to enrich the knowledge about the family and social circumstances associated to the Mexican family caregivers.

Use of a modified expander during rapid maxillary expansion in adults: an in vitro and finite element study.

PURPOSE: This preliminary study was performed to evaluate a proposed maxillary expansion treatment method for adults with fused intermaxillary sutures. MATERIALS AND METHODS: This study was performed in three Thiel-fixed skulls from older female cadavers with a microimplant-supported expansion screw. This modified expansion screw was mounted on the palatine process with microimplants and activated every 15 to 20 seconds with an activation key until the intermaxillary suture ruptured. A strain gauge was bonded to the expansion screw and calibrated so it could be used as a force sensor device. Rupture of the intermaxillary suture was indicated by a sudden drop in the registered force, through visible opening of the suture, and via computed tomographic data. Finite element simulations were performed, which led to the experimental testing. RESULTS: Rupture of the intermaxillary suture was achieved in all three experiments with the microimplant-supported screw. The strain measurement on one of the expansion screws resulted in an expansion force of 86 N. Finite element simulations showed a high tensile stress concentration exerted by the microimplant-supported expansion screw on the intermaxillary suture. CONCLUSION: The applied expansion force led to high tensile stress concentrations, mainly on the intermaxillary sutures, resulting in the opening of fused intermaxillary sutures. This method may help adults to be treated by an orthodontist, thereby avoiding surgical intervention.

Histological evidence for muscle insertion in extant amniote femora: implications for muscle reconstruction in fossils.

Since the 19th century, identification of muscle attachment sites on bones has been important for muscle reconstructions, especially in fossil tetrapods, and therefore has been the subject of numerous biological and paleontological studies. At the microscopic level, in histological thin sections, the only features that can be used reliably for identifying tendon-bone or muscle-tendon-bone interactions are Sharpey's fibers. Muscles, however, do not only attach to the bone indirectly with tendons, but also directly. Previous studies failed to provide new indicators for muscle attachment, or to address the question of whether muscles with direct attachment can be identified histologically. However, histological identification of direct muscle attachments is important because these attachments do not leave visible marks (e.g. scars and rugosities) on the bone surface. We dissected the right hind limb and mapped the muscle attachment sites on the femur of one rabbit (Oryctolagus cuniculus), one Alligator mississippiensis, and one turkey (Meleagris cuniculus). We then extracted the femur and prepared four histological thin sections for the rabbit and the turkey and five histological thin sections for the alligator. Sharpey's fibers, vascular canal orientation, and a frayed periosteal margin can be indicators for indirect but also direct muscle attachment. Sharpey's fibers can be oriented to the cutting plane of the thin section at high angles, and two Sharpey's fibers orientations can occur in one area, possibly indicating a secondary force axis. However, only about 60% of mapped muscle attachment sites could be detected in thin sections, and frequently histological features suggestive of muscle attachment occurred outside mapped sites. While these insights should improve our ability to successfully identify and reconstruct muscles in extinct species, they also show the limitations of this approach.

Life history of Rhamphorhynchus inferred from bone histology and the diversity of pterosaurian growth strategies.

BACKGROUND: Rhamphorhynchus from the Solnhofen Limestones is the most prevalent long tailed pterosaur with a debated life history. Whereas morphological studies suggested a slow crocodile-like growth strategy and superprecocial volant hatchlings, the only histological study hitherto conducted on Rhamphorhynchus concluded a relatively high growth rate for the genus. These controversial conclusions can be tested by a bone histological survey of an ontogenetic series of Rhamphorhynchus. METHODOLOGY/PRINCIPAL FINDINGS: Our results suggest that Bennett's second size category does not reflect real ontogenetic stage. Significant body size differences of histologically as well as morphologically adult specimens suggest developmental plasticity. Contrasting the 'superprecocial hatchling' hypothesis, the dominance of fibrolamellar bone in early juveniles implies that hatchlings sustained high growth rate, however only up to the attainment of 30-50% and 7-20% of adult wingspan and body mass, respectively. The early fast growth phase was followed by a prolonged, slow-growth phase indicated by parallel-fibred bone deposition and lines of arrested growth in the cortex, a transition which has also been observed in Pterodaustro. An external fundamental system is absent in all investigated specimens, but due to the restricted sample size, neither determinate nor indeterminate growth could be confirmed in Rhamphorhynchus. CONCLUSIONS/SIGNIFICANCE: The initial rapid growth phase early in Rhamphorhynchus ontogeny supports the non-volant nature of its hatchlings, and refutes the widely accepted 'superprecocial hatchling' hypothesis. We suggest the onset of powered flight, and not of reproduction as the cause of the transition from the fast growth phase to a prolonged slower growth phase. Rapidly growing early juveniles may have been attended by their parents, or could have been independent precocial, but non-volant arboreal creatures until attaining a certain somatic maturity to get airborne. This study adds to the understanding on the diversity of pterosaurian growth strategies.

In-vitro results of rapid maxillary expansion on adults compared with finite element simulations.

This study was mainly performed to investigate the effects of high maxillary expansion forces on the skull with fresh and thiel-fixed human skulls. The maxillary suture was not weakened except in one experiment. This study compares the strain measured on the zygomatic process of the skull with the results of a finite element model generated for this purpose. An increasing transversal force was applied on the alveolar process (teeth) until rupture. Strain on the zygomatic process, maxilla displacement and the expanding forces were registered. The results of this study show linear material behaviour of the skull before rupture. The highest stress during the experiments and FE simulation was observed on the alveolar process. Conclusions of this study are the necessity of the existence of appropriate models and that female specimens seem to rupture at a lower force than male ones. Both male and female specimens show a similar linear behaviour in the force/strain curve within each gender group. The probability of maxillary suture opening in adults during ultra-rapid maxillary expansion with tooth anchorage is very low. Complications and unwanted rupture could occur.

Inhibition of HER-2 by three independent targeting strategies increases paclitaxel resistance of SKOV-3 ovarian carcinoma cells.

Current treatment options for ovarian cancer, which is one of the most widespread gynecological malignancies, are limited, mainly because patients with advanced-stage disease often develop resistance to chemotherapeutics. In breast cancer cells, several studies suggest that overexpression of the human epidermal growth factor receptor-2 (HER-2) leads to increased resistance against certain, but not all cytotoxic drugs. In ovarian carcinoma, conflicting data on the correlation of HER-2 expression and tumor cell sensitivity exist. In this paper, we explore the role of HER-2 expression and signaling levels pertaining to paclitaxel (Taxol) chemoresistance by applying three different and independent strategies in SKOV-3 ovarian carcinoma cells. Firstly, we show that treatment with the HER-2 inhibitory antibody trastuzumab (Herceptin), which is well established in tumor therapy, results in markedly increased, rather than decreased, cellular paclitaxel resistance. Next, we present two newly developed low molecular weight inhibitors of HER-2 tyrosine kinase activity, D-69491 and D-70166. With both drugs, the decrease in cellular paclitaxel sensitivity upon HER-2 inhibition is confirmed. Finally, for more detailed analysis we stably downregulate HER-2 expression by ribozyme-targeting. Using clonal ribozyme-transfected SKOV-3 cells with different residual HER-2 levels, we establish a 'HER-2 gene dose effect' of paclitaxel cytotoxicity. We show that this effect is due to differential induction of apoptosis and differential cell cycle inhibition by paclitaxel. Finally, paclitaxel- or HER-2-mediated alterations in the phosphorylation of MAP kinases p42/44, Stress-activated protein kinase/Jun-terminal kinase (SAPK/JNK), and p38, and effects on the activation of caspase-3, caspase-7, and bcl-2 are discussed. We conclude that paclitaxel cytotoxicity in SKOV-3 cells is 'HER-2 dose-dependent' and identify cell proliferation as one underlying cellular event of this effect.

Reconstructing the evolution of the respiratory apparatus in tetrapods.

The structural type of a lung for animals that are derived from a single ancestral group can be characterized using extant phylogenetic bracketing. Functional morphological approximation can then be used to provide further information on the functional attributes. Combining information from diverse sources, plausible explanations are deduced for the respiratory apparatus of extinct species. The air-breathing apparatus of tetrapods has its origin in gill breathing. The lungs of the first tetrapods were probably long and consisted of a single series of parenchyma-filled chambers, arranged along an intrapulmonary duct. The duct gave rise to a broad central lumen in anurans. In amniotes a cartilaginous reinforcement evolved. The septate nature of the gas-exchange tissue (parenchyma) is recognizable in all tetrapods except birds. Active expiration began with the origin of transverse body wall musculature in amphibians, whereas active, negative-pressure inspiration is seen only in amniotes. The functional transition of trunk musculature from locomotor to respiratory is most complete in birds.

Cytotoxicity of the novel anti-cancer drug rViscumin depends on HER-2 levels in SKOV-3 cells.

rViscumin is a recombinant mistletoe lectin under clinical investigation as new anti-cancer drug. The relationship between oncogene, e.g., HER-2/neu (c-erbB2) receptor activation and tumor cell chemosensitivity, is of considerable importance to better predict the response to chemotherapy. Here, we analyze the cellular and molecular effects of HER-2 expression on rViscumin chemotoxicity in SKOV-3 cells. We show that selective depletion of HER-2 by ribozyme-targeting markedly decreases cellular sensitivity towards rViscumin. These findings are confirmed by treatment with the well-established inhibitory HER-2 antibody trastuzumab (Herceptin). Using clonal ribozyme-transfected cell lines, we establish a 'HER-2 gene dose' dependence of rViscumin cytotoxicity, which is due to differential induction of apoptosis and is not mediated by cell cycle alterations or altered cellular rViscumin binding/internalization. We further demonstrate an rViscumin-mediated, HER-2-dependent down-regulation of bcl-2 and the dose-dependent activation of members of the MAPK family, p42/44, SAPK/JNK, and p38, but not of caspases-3 and -7.